This Program Project is directed toward the challenge of transferring genes to progenitor and differentiated cells relevant to disorders of the heart, lung, and blood, a challenge that can be successfully overcome ony by under-standing the biology of gene transfer to these target cells, and the consequences of modifying the genetic reper-toire of one or more cell types in the relevant target organs. To accomplish this, the Program Project is con-structed to bring together senior investigators at CUMC, SKI, and The Rockefeller University with overlapping interests in gene transfer to progenitor and differentiated cells, and focus the activities o their laboratories, to-gether with existing gene therapy core facilities, towards and integrated effort relevant to gene therapy of disor-ders of the heart, lung and blood. The program Project is comprised of five projects, six core laboratories, and two pilot projects. The five projects include: (1) studies of the regulation of cardiac myocyte cell division in the embryo relevant to gene therapy in the adult myocardium: (2) gene transfer to hematopoietic progenitor cells to stimulate stem cell and lineage-specific growth and differentiation: (3) the biology of gene transf to precursor, resting and activated alveolar macrophages: (4) the biologic determinants of gene transfer to hematopoietic pro-genitor cells, with a focus on transcriptional and chromatin determinants relevant to long term expression in the context of a housekeeping gene (G6PD) that may confer selective growth advantage to genetically corrected cells in the deficient host; and (5) the development of a chimeric gene transfer system, relevant to progenitor and differentiated cells, that combines the advantages of effective transient gene transfer with adenovirus vectors and the integrating potential of adeno-associated virus. The four core laboratories all established, include: Core A - DNA viral vectors (adenovirus, adeno- associated virus, herpesvirus); Core B - retrovirus vectors; Core C - cell biology; Core F - administration. The two pilot projects (Core G) include: pilot 1- angiogenesis in the central nervous system for the prophylaxis and therapy of stroke; and Pilot 2-adeno-associated virus vectors coding for apolipoprotein E (apoE) to modulate cholesterol metabolism and central nervous system adnormalities in apoE deficient mice.